Camoranesi began his career in Argentina in 1995, where he played for Aldosivi and Banfield , also having spells in Mexico with Santos Laguna and Cruz Azul, and in Uruguay with Wanderers. In 2000, he moved to Italy, joining Verona, where his performances earned him a transfer to defending Serie A champions Juventus in 2002. Camoranesi won the league title and the Supercoppa Italiana in his first season with the club, also reaching the Champions League final; he spent most of his career with the Turin side, also winning a second Supercoppa Italiana during his eight seasons with the Bianconeri. In 2010, he joined German side VfB Stuttgart for a season, before returning to Argentina to play for Lanús, and subsequently Racing Club, where he retired in 2014. Following his retirement, Camoranesi began his managerial career later that year, and has since coached Mexican club Coras de Tepic and Argentine side Tigre.

Camoranesi had always been a big fan of the Argentinian club River Plate growing up, but as a youngster, he played in the squad of Club Atlético Aldosivi. Aldosivi is situated in Mar del Plata just 100 miles away from Camoranesi's birthplace of Tandil. However, he moved to Mexico to begin his professional playing career at Santos Laguna during the 1995–96 season and scored one goal in 13 games for the team; Santos Laguna fans nicknamed him "El Cholo".

More travels came for the young Argentine the following year, as he moved to Uruguayan club Montevideo Wanderers briefly, before returning to his homeland to play for Banfield, solidifying himself as an impressive attacking right midfielder, while playing 38 games with 16 goals.

He caught the attention of Italian Serie A side Verona by scoring 21 goals in 79 games with Cruz Azul, an impressive achievement for a midfielder. He moved to Italy in 2000, signing with Verona where he played for two years.

In 2002, Camoranesi was signed on a co-ownership deal; initially Juventus agreed a price of €1[3] in cash plus player deal (which Max Vieri was sold for €517,000 (or 1 billion lire) plus €2.324 million cash (or 4.5 billion lire cash)) On 26 June 2003, he was signed outright by the Bianconeri on a permanent basis for an additional fee of €5 million; this was the same day Juventus signed Marco Di Vaio in similar deal.

Despite his agent Sergio Fortunato linking the player to clubs such as Lyon, Valencia, and Liverpool over the summer of 2006, following Juventus's relegation, Camoranesi made an announcement himself in September, pledging loyalty to Juventus "In January, I will not ask to be sold; I'm happy to stay here.",[4] he stated.

Camoranesi contributed to a number of notable goals when Juventus played in Serie B after the relegation. Against Lecce in April 2007, he performed an impressive piece of skill similar to a Cruyff turn, turning the ball through a defender's legs on the wing, before retrieving it to help set up Juventus's first goal of the match. Later in the match, he scored his side's third; Camoranesi took the ball past three Lecce defenders, before hitting the ball from the edge of the box, with his left foot into the top corner.[5] Just days before he had scored a header in the 2–0 victory against close title contenders Napoli. His original shirt number was 16, but was changed to 8 for the 2007–08 season. He changed back to number 16 from 8 after just one season. Despite suffering several injuries during the 2007–08 season, he was a very important and influential player in Juventus' return season. He also won the Guerin d'Oro award, as the player with the highest average rating, for his performances throughout the season.

Camoranesi had an impressive pre-season before the up-and-coming 2008–09Serie A season. After struggling in the first few games in the start of Serie A season 2009–10, Camoranesi came back strongly and proved to be one of Juventus' most important players. He managed to get his name on ths scoresheet too, scoring the solitary goal against Maccabi Haifa in the Champions League, as well as a brace in a 5–2 win over Atalanta.

On 31 August 2010, Camoranesi signed a one-year contract with Stuttgart as a free agent.[6] His contract with Juventus was mutually terminated on the same day.[7] On 26 January 2011, his contract with Stuttgart was mutually terminated, with Camoranesi admitting that he "just didn't fit in the club sporting wise, although he liked the team, the people and the city." He expressed a desire to continue his career in Argentina.[8]

On 2 February 2011, Camoranesi signed a two-year contract with Lanús with the option to coach youth players if he decides to retire.[9] In October 2011, Camoranesi made headlines for kicking an opponent in the head. In a match against Racing Club, Camoranesi fouled Patricio Toranzo and was shown a red card by the referee. Instead of walking off, Camoranesi ran back and kicked Toranzo in the head while Toranzo was still lying on the ground. Toranzo later commented that Camoranesi is "not much of a man, just a coward" and suggested Camoranesi would need to see a psychiatrist for his violent behaviour. Camoranesi faced a long ban from football for this incident.

On 20 July 2012, Camoranesi signed in for Argentine side Racing Club from Avellaneda. On 13 June 2013, He announced that he would retire from football at the end of the season in June, although rumours have circulated he could be close to joining Leicester to link up with Argentine midefield Esteban Cambiasso[10][11][12] On 16 March 2014, Mauro was subbed on in the 68th minute for teammate Rodrigo De Paul, his side lost 0–2 away to Newell's Old Boys, a club which saw former Juventus F.C. teammate David Trezeguet score the second goal of the game in the 83rd minute. This turned out to be Camoranesi's last game in his career.

Camoranesi was eligible for Italian citizenship through a great-grandfather, Luigi, who in 1873 emigrated from Potenza Picena, in Italy's Marche region, to Argentina.[13][14] His dual citizenship made him eligible to play for either Argentina or Italy, but the Azzurri showed interest in him first and, on 12 February 2003, he made his international debut in a friendly match against Portugal, which Italy won 1–0, under former coach Giovanni Trapattoni. Camoranesi played for Italy at UEFA Euro 2004 and was also part of Marcello Lippi's Italy team which won the 2006 FIFA World Cup. He has been capped 55 times by Italy and has scored four goals, the first of which came in Italy's 2006 World Cup qualifier away to Belarus on 7 September 2005, which the Italians won 4–1.

During the 2006 World Cup Finals in Germany, he admitted the reason for not singing Italy's national anthem before their matches was because he did not know the words,[15] although he could be seen singing (at least a part of) the anthem during the World Cup celebrations in Circus Maximus on 10 July 2006. Camoranesi was not the first Juventus player born in Argentina to play for Italy; Omar Sivori played for the azzurri, as well as Luis Monti and Raimundo Orsi who also won the World Cup while playing for Juventus.

At the end of 2006 FIFA World Cup Final match in Germany, in which Italy defeated France 5–3 in a penalty shoot-out, Camoranesi had teammate Massimo Oddo chop off a large chunk of his long hair as the rest of the squad danced around them in a circle. Camoranesi then went up to the camera and dedicated the triumph by saying in Spanish: "Para los pibes del barrio" (For the guys from the neighbourhood).[16]

Camoranesi commented in an interview in regards to the World Cup victory: "I feel Argentine but I have defended the colours of Italy, which is in my blood, with dignity. That is something nobody can take away."[17]

Camoranesi was a dynamic, hard-working, and skilful midfielder, who usually deployed on the right wing, or on occasion as a central or attacking midfielder behind the strikers.[18] He was a quick, energetic, and technically gifted player, with excellent ball control, who excelled at dribbling and beating players in one on one situations.[18] He was also gifted with good vision, crossing and passing ability with his right foot, which allowed him to create chances for his team mates.[19] In addition to these characteristics, he also had an accurate and powerful shot, and was known for his offensive and defensive contribution.[19] A tenacious winger, throughout his career, he was however criticised for his aggression and lack of discipline at times, which caused him to pick up unnecessary bookings.[19]